title: Heat shock protein90 in lobular neoplasia of the breast.
abstract: BACKGROUND
  Heat shock protein 90 (Hsp90) overexpression has been implicated in breast carcinogenesis, with putative prognostic and therapeutic implications. The purpose of this study is to evaluate the immunohistochemical expression of Hsp90 and to examine whether Hsp90 expression is associated with estrogen receptor alpha (ER-alpha) and beta (ER-beta) immunostaining in lobular neoplasia (LN) of the breast.
  
  
  METHODS
  Tissue specimens were taken from 44 patients with LN. Immunohistochemical assessment of Hsp90, ER-alpha and ER-beta was performed both in the lesion and the adjacent normal breast ducts and lobules; the latter serving as control. As far as Hsp90 evaluation is concerned: i) the percentage of positive cells, and ii) the intensity was separately analyzed. Additionally, the Allred score was adopted and calculated. Accordingly, Allred score was separately evaluated for ER-alpha and ER-beta. The intensity was treated as an ordinal variable-score (0: negative, low: 1, moderate: 2, high: 3). Statistical analysis followed.
  
  
  RESULTS
  Hsp90 immunoreactivity was mainly cytoplasmic in both the epithelial cells of normal breast (ducts and lobules) and LN. Some epithelial cells of LN also showed nuclear staining, but all the LN foci mainly disclosed a positive cytoplasmic immunoreaction for Hsp90. In addition, rare intralobular inflammatory cells showed a slight immunoreaction. The percentage of Hsp90 positive cells in the LN areas was equal to 67.1 +/- 12.2%, whereas the respective percentage in the normal adjacent breast tissue was 69.1 +/- 11.6%; the difference was not statistically significant. The intensity score of Hsp90 staining was 1.82 +/- 0.72 in LN foci, while in the normal adjacent tissue the intensity score was 2.14 +/- 0.64. This difference was statistically significant (p = 0.029, Wilcoxon matched-pairs signed-ranks test). The Hsp90 Allred score was 6.46 +/- 1.14 in the LN foci, significantly lower than in the normal adjacent tissue (6.91 +/- 0.92, p = 0.049, Wilcoxon matched-pairs signed-ranks test). Within the LN foci, the Hsp90 Allred score was neither associated with ER-alpha, nor with ER-beta percentage.
  
  
  CONCLUSIONS
  Hsp90 was lower in LN foci both at the level of intensity and Allred score, a finding contrary to what might have been expected, given that high Hsp90 expression is detected in invasive breast carcinomas. Hsp90 deregulation does not seem to be a major event in LN pathogenesis.
authors.affiliation: 1st Department of Propaedeutic Surgery, Breast Unit, Hippokratio Hospital, University of Athens, Athens, Greece. florazagouri@yahoo.co.uk
authors.forename: Flora
authors.initials: F
authors.lastname: Zagouri
authors.forename: Afrodite
authors.initials: A
authors.lastname: Nonni
authors.forename: Theodoros N
authors.initials: TN
authors.lastname: Sergentanis
authors.forename: Christos A
authors.initials: CA
authors.lastname: Papadimitriou
authors.forename: Nikolaos V
authors.initials: NV
authors.lastname: Michalopoulos
authors.forename: Andreas C
authors.initials: AC
authors.lastname: Lazaris
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.forename: George C
authors.initials: GC
authors.lastname: Zografos
mesh_terms: D000328:Adult; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018275:Carcinoma, Lobular / Q000378:metabolism* / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology; D008875:Middle Aged
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D018841:HSP90 Heat-Shock Proteins